Elevated Prolactin Research Articles

FRI398 A Case Of Secondary Amenorrhea: Is It Only PCOS To Blame?

Abstract Disclosure: P. Panjawatanan: None. S. Riahi: None. S.S. Chaidarun: None. Background: One of the most common causes of secondary amenorrhea is PCOS (polycystic ovary syndrome) which accounts for 30% of the cases. Though not as common, hyperprolactinemia similarly contributes to the condition. Here we describe a patient who presented with secondary amenorrhea from medication-induced hyperprolactinemia with underlying PCOS. Clinical Case: A 31-year-old female with a past medical history of bipolar disorder, hypothyroidism, and PCOS, presented with secondary amenorrhea. The patient started menarche at 11 years old and was diagnosed with PCOS a year later due to irregular menses and hirsutism. The estrogen-containing pill was prescribed, but she developed a blood clot due to Factor V Leiden thrombophilia. She was taking atomoxetine, lithium, mirtazapine, and olanzapine for her psychiatric issues and recently started on paliperidone last year. She reported no period in the past two years after stopping oral contraception. Pregnancy was ruled out. She tried progesterone challenge test but did not have any flow. Transvaginal ultrasound showed thin endometrium. She had IUD placed for contraception. Laboratory testing four months and one year after starting paliperidone showed prolactin of 79.2 ng/mL and 110 ng/mL consecutively. The patient reported headaches but denied galactorrhea or visual loss. There are no signs or symptoms of Cushing’s disease, acromegaly, or hypothyroidism. Further workup showed TSH 1.52 mcIU/mL, estradiol 16 pg/mL, FSH 5.6 mIU/mL, 17-OH progesterone <40 ng/dL, total testosterone 14 ng/dL, ACTH 11 pg/mL, IGF-1 z-score -0.67 SD. MRI brain was ordered, which ruled out pituitary adenoma. Repeat prolactin level remained elevated at 87.7 ng/mL without treatment. We concluded that the patient has secondary amenorrhea from PCOS and antipsychotic-induced hyperprolactinemia. Patient was referred to a psychiatrist for antipsychotic medication changes. Conclusion: Antipsychotics, typically first-generation, are known to cause hyperprolactinemia due to their dopamine-antagonist effect. Prolactin level ranging from 25-100 ng/mL is seen in medication-induced hyperprolactinemia, while particular medication like risperidone and phenothiazines can raise the level to more than 200 ng/mL. Newer agent paliperidone has been reported to induce hyperprolactinemia similarly to risperidone which explains significant prolactin elevation in this patient. Hyperprolactinemia poses a risk for hypogonadism due to suppressed pituitary-gonadal axis, resulting in anovulation and bone loss. Estrogen therapy is considered an adjunct to help with hypogonadism. However, it is contraindicated in patients with thrombophilia. The guideline recommends switching to a low-risk antipsychotic agent if feasible. Despite having an established diagnosis of PCOS, it is important to consider other secondary causes of amenorrhea which may occur concomitantly. Presentation: Friday, June 16, 2023

Normal intellectual ability and hyperprolactinemia as unique clinical manifestations of congenital hypothyroidism: A case report and review of hypotheses.

Congenital hypothyroidism is the deficiency of thyroid hormone in infants and hyperprolactinemia is frequently observed. Previously reported cases typically involve intellectual disability, highlighting this particular unique case report to the first reported patient demonstrating normal intellectual ability despite experiencing growth and gonad dysfunction. This study aims to present a case and review medical hypotheses related to the patient's condition. A 19-year-old female presented with a chief complaint of irregular menstruation for up to 40 days or not occurring at all. The patient experienced the first menstruation at the age of 16 years old. The patient's height was 133 cm, body weight 40 kg, and body mass index 22.61 kg/m2; other family members were normal. Physical examination showed no abnormalities, and laboratory examination showed suppressed serum free T4 (FT4) level (6.41 pmol/L), elevated thyroid stimulating hormone (TSH) level (333.700 µIU/mL), and elevated prolactin hormone level (32.03 ng/mL). Ultrasound of the thyroid gland found hypoplasia of the left and right thyroid glands. The patient was a college student enrolled in a public national university and had never complained about academic performance throughout the patient's education. The patient was diagnosed with congenital hypothyroidism and hyperprolactinemia. The patient was administered up to 100 µg daily of oral levothyroxine, which improved the patient's menstrual cycles. The patient's delayed diagnosis may be attributed to central congenital hypothyroidism being underdiagnosed. We hypothesized that thyroid-releasing hormone receptor (TRHR) gene mutation might contribute to the underlying cause of hyperprolactinemia and normal intellectual ability of the patient. Further study on the significance of TRHR gene mutations in congenital hypothyroidism is required to improve diagnosis and treatment.

Serum Prolactin Level in Women with Systemic Lupus Erythematosus and its Correlation with Disease Activity

Abstract Background: In the last decade, evidence supports the hypothesis that the prolactin (PRL) hormone plays an important role in systemic lupus erythematosus (SLE) clinical expression and pathogenesis. Objective: To evaluate the presence, clinical, and serological significance of elevated serum PRL in women with SLE. Materials and Methods: A case–control study included 30 women with SLE; with mean age and disease duration were 33.15 ± 6.7 and 10.9 ± 1.9, respectively, and 30 age-matched apparently healthy subjects served as controls. All patients were subjected to clinical and serological evaluation. Disease activity was measured using the SLE Disease Activity Index. Serum PRL level was estimated for all the participants. Results: Serum PRL levels were 36.2 ± 15.8 ng/ml and 8.9 ± 4.4 ng/ml in patients with SLE and controls, respectively. Malar rash, photosensitivity, and arthritis were associated with elevated serum PRL. Positive antinuclear antibodies ANA and low complements were associated with a high serum PRL level. In addition, 18 (85.7%) patients with high disease activity have hyperprolactinemia, while only 3 (14.3%) patients with high disease activity have a normal range of serum PRL levels. Conclusion: SLE patients were associated with higher serum PRL levels than the control group. There was a significant relationship between serological status and hypocomplementemia with high serum PRL levels. In addition, there was a significant relationship between active disease and hyperprolactinemia.

Phytocompositions of ayurvedic medicine in the restoration of menstrual health in women of early reproductive age who have survived moderate and severe form of COVID-19

Research objectives: to evaluate the effectiveness of phytotherapy in the treatment of menstrual health disorders in women of early reproductive age after a moderate and severe form of the coronavirus disease.Material and methods. 104 women of early reproductive age with menstrual health disorders that occurred 3 months later after moderate or severe COVID-19 were under observation and 34 gynecologically and somatically healthy women of the control group who did not suffer from COVID-19. Female patients with COVID-19 were randomly divided into two groups: the main group (n=53) and the comparison group (n=51). The performed examination included: study of complaints, general and gynecological anamnesis, physical and gynecological examination, ultrasound examination of pelvic organs, determination of hormonal profile. All patients with COVID-19 received a comprehensive rehabilitation program, which included diet therapy, vitamin and mineral complexes, psychotherapy. In addition to the complex rehabilitation program patients of the main group received ayurvedic phytocompositions Femicycle or Femimens for 6 months.Results. It has been established that the moderate and severe course of the coronavirus infection affects the reproductive system of early reproductive aged women and leads to menstrual health disorders, among which irregular menstruation, premenstrual syndrome and dysmenorrhea dominate. Levels of pituitary, adrenal, ovarian and thyroid serum hormones were within the reference norm in most cases, but have statistically significant deviations from similar indicators of healthy control women who did not have COVID-19. One-third of women of early reproductive age after moderate to severe COVID-19 had elevated prolactin levels. Ayurvedic phytocompositions Femicycle and Femimens in a comprehensive rehabilitation program for post-COVID menstrual health disorders led to a faster recovery of menstrual health and a full hormonal recovery.Conclusions. Ayurvedic phytocompositions Femicycle and Femimens are effective and safe naturopathic drugs for restoring menstrual health in women of early reproductive age after experiencing moderate to severe COVID-19.

Frequency of drug-associated hyperprolactinaemia: a single-center retrospective study

Objectives: One of the causes of hyperprolactinaemia (HP) is drug-associated HP (DAHP). In this study, it was planned to investigate the frequency of DAHP. Methods: In this study, a retrospective review of 296 individuals referred to the endocrinology outpatient clinic between June 2013 and March 2018 due to elevated prolactin (PRL) was performed. Results: Of the 296 patients included in the study, 140 (47.3%) had HP (+), 80 (27.0%) had HP (-), 27 (9.1%) had DAHP and other causes (16.6%). The causes of DAHP were as follows; sulpiride in 7 (25.9%) patients, risperidone in 6 (22.2%), amisulpride in 4 (14.8%), domperidone in 3 (11.1%), haloperidol in 2 (7.4%), paliperidone, olanzapine, escitalopram, duloxetine and otilonium bromide in one patient each. PRL levels in the DAHP group were higher than in the HP (-) group (respectively; median 114.6 [interquartile range (IQR): 144.0], median 35 [IQR 37.3], p < 0.001). Patients with DAHP had an increased frequency of symptoms compared to the HP (-) group (oligomenorrhoea; 42.3%, 16.4%, p = 0.007, galactorrhoea; 53.8%, 30.1%, p = 0.028, respectively). PRL levels were higher and the frequency of clinical signs was higher in sulpiride than risperidone (PRL; median 195.0 [IQR 99.0], median 72.0 [IQR 57.9], p = 0.022, oligomenorrhoea; 100%, 20%, p = 0.010, respectively). Conclusions: One of the 3 most common causes of patients referred for HP is DAHP and the most common cause of DAHP is anti-psychotic drugs. Sulpiride causes a higher rate of elevated PRL and frequency of clinical findings compared to other drugs.

The relationship between metabolic stress and Anti- Müllerian hormone (AMH) in women hospitalized in intensive care units

Objective: Our study aimed to investigate the levels of anti-Müllerian hormone (AMH) to determine ovarian reserve in women in intensive care units experiencing metabolic and physiological stress. Materials and Methods: For this purpose, 37 women were hospitalized in the intensive care unit (ICU) of Siirt Training and Research Hospital between November 2022 and February 2023. The same number of healthy control groups were included in the study. Patient selection was based on acute physiology and chronic health assessment (APACHI II) score and injury severity score (ISS).Anti-müllerian hormone (AMH), follicle stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2) thyroid stimulating hormone (TSH), triiodothyronine (T3), tetraiodothyronine (T4), adrenocorticotropic hormone (ACTH), cortisol. , prolactin, C-reactive hormone (CRP) serum levels were examined Results: There was no significant difference in mean age between intensive care patients (29.3±8.3 , n=37) and control group (28.0±0.0, n=37) (p=0.349). A statistically significant difference was found between the AMH values between the patients hospitalized in the intensive care unit and the control group (p=0.012).AMH values were significantly lower in ICU patients. However, the T3 value was observed to be significantly lower in ICU patients compared to the control group (p < 0.0001). Additionally, prolactin, CRP, and cortisol values were found to be statistically significantly higher. Conclusion: This study revealed a significant decrease in anti-Müllerian hormone (AMH) levels among women experiencing metabolic and physiological stress in intensive care units. The lowered AMH levels suggest a potential impact on ovarian reserve in such conditions. Additionally, the observation of reduced T3 levels in ICU patients could indicate thyroid function alterations during times of stress. The elevated prolactin, CRP, and cortisol levels further underscore the physiological disruptions experienced by ICU patients. These findings emphasize the importance of considering hormonal and metabolic changes in critically ill women, particularly in relation to their ovarian health. Further research is warranted to elucidate the intricate mechanisms underlying these hormonal alterations and their potential long-term implications.

Schizophrenia plausible protective effect of microRNA-137 is potentially related to estrogen and prolactin in female patients.

Schizophrenia (SCZ) is a serious chronic mental disorder. Our previous case-control genetic association study has shown that microRNA-137 (miR-137) may only protect females against SCZ. Since estrogen, an important female sex hormone, exerts neuroprotective effects, the relationship between estrogen and miR-137 in the pathophysiology of SCZ was further studied in this study. Genotyping of single-nucleotide polymorphism rs1625579 of miR-137 gene in 1,004 SCZ patients and 896 healthy controls was conducted using the iMLDR assay. The effect of estradiol (E2) on the miR-137 expression was evaluated on the human mammary adenocarcinoma cell line (MCF-7) and the mouse hippocampal neuron cell line (HT22). The relationships between serum E2, prolactin (PRL), and peripheral blood miR-137 were investigated in 41 SCZ patients and 43 healthy controls. The miR-137 and other reference miRNAs were detected by real-time fluorescent quantitative reverse transcription-PCR. Based on the well-known SNP rs1625579, the distributions of protective genotypes and alleles of the miR-137 gene were not different between patients and healthy controls but were marginally significantly lower in female patients. E2 upregulated the expression of miR-137 to 2.83 and 1.81 times in MCF-7 and HT22 cells, respectively. Both serum E2 and blood miR-137 were significantly decreased or downregulated in SCZ patients, but they lacked expected positive correlations with each other in both patients and controls. When stratified by sex, blood miR-137 was negatively correlated with serum E2 in female patients. On the other hand, serum PRL was significantly increased in SCZ patients, and the female patients had the highest serum PRL level and a negative correlation between serum PRL and blood miR-137. The plausible SCZ-protective effect of miR-137 may be female specific, of which the underlying mechanism may be that E2 upregulates the expression of miR-137. This protective mechanism may also be abrogated by elevated PRL in female patients. These preliminary findings suggest a new genetic/environmental interaction mechanism for E2/miR-137 to protect normal females against SCZ and a novel E2/PRL/miR-137-related pathophysiology of female SCZ, implying some new antipsychotic ways for female patients in future.

Impaired Prolactin-Lowering Effects of Metformin in Women with Polycystic Ovary Syndrome.

The effect of metformin on prolactin concentration seems to be sex-dependent. The aim of this study was to determine whether the androgen status modulates the impact of metformin on plasma prolactin levels in women. This study included two matched groups of prediabetic women with hyperprolactinemia: 25 with PCOS and 25 control subjects with androgen levels within the reference range and with normal ovarian morphology. Glucose homeostasis markers, prolactin, the remaining anterior pituitary hormones, sex hormones, SHBG and IGF-1 were determined before and after six months of metformin treatment. At baseline, both groups differed in LH, LH/FSH ratio, testosterone, FAI, DHEA-S, androstenedione and estradiol. Although metformin improved insulin sensitivity and increased SHBG in both study groups, these effects were more pronounced in control subjects than in women with PCOS. In control subjects, the drug decreased total and monomeric prolactin and increased LH. In women with PCOS, metformin reduced LH, LH/FSH ratio, testosterone and FAI. In the control group, the impact on total and monomeric prolactin positively correlated with their baseline levels and with the degree of improvement in insulin sensitivity, as well as negatively correlated with testosterone and FAI. In women with PCOS, treatment-induced changes in testosterone and FAI positively correlated with the changes in LH and LH/FSH ratio. The obtained results suggest that the prolactin-lowering properties of metformin are less pronounced in women with coexisting PCOS than in women with elevated prolactin levels, probably owing to the increased production of endogenous testosterone.

Identifying Suitable Targets for Alzheimer's Disease and Other Eight Common Neurological Disorders Using the Human Plasma Proteome: A Mendelian Randomization Study.

Neurological disorders, such as Alzheimer's disease (AD), comprise a major cause of health-related disabilities in human. However, biomarkers towards pathogenesis or novel targets are still limited. To identify the causality between plasma proteins and the risk of AD and other eight common neurological diseases using a Mendelian randomization (MR) study. Exposure data were obtained from a genome-wide association study (GWAS) of 2,994 plasma proteins in 3,301 healthy adults, and outcome datasets included GWAS summary statistics of nine neurological disorders. Inverse variance-weighted MR method as the primary analysis was used to estimate causal effects. Higher genetically proxied plasma myeloid cell surface antigen CD33 level was found to be associated with increased risk of AD (odds ratio [OR] 1.079, 95% confidence interval [CI] 1.047-1.112, p = 8.39×10-7). We also discovered the causality between genetically proxied elevated prolactin and higher risk of epilepsy (OR = 1.068, 95% CI = 1.034-1.102; p = 5.46×10-5). Negative associations were identified between cyclin-dependent kinase 8 and ischemic stroke (OR = 0.927, 95% CI = 0.896-0.959, p = 9.32×10-6), between neuralized E3 ubiquitin-protein ligase 1 and migraine (OR = 0.914, 95% CI = 0.878-0.952, p = 1.48×10-5), and between Fc receptor-like protein 4 and multiple sclerosis (MS) (OR = 0.929, 95% CI = 0.897-0.963, p = 4.27×10-5). The findings identified MR-level protein-disease associations for AD, epilepsy, ischemic stroke, migraine, and MS.

Levodopa-refractory hyperprolactinemia and pituitary findings in inherited disorders of biogenic amine metabolism.

Elevated serum prolactin concentrations occur in inherited disorders of biogenic amine metabolism because dopamine deficiency leads to insufficient inhibition of prolactin secretion. This work from the International Working Group on Neurotransmitter Related Disorders (iNTD) presents the results of the first standardized study on levodopa-refractory hyperprolactinemia (LRHP; >1000 mU/L) and pituitary magnetic resonance imaging (MRI) abnormalities in patients with inherited disorders of biogenic amine metabolism. Twenty-six individuals had LRHP or abnormal pituitary findings on MRI. Tetrahydrobiopterin deficiencies were the most common diagnoses (n = 22). The median age at diagnosis of LRHP was 16 years (range: 2.5-30, 1st-3rd quartiles: 12.25-17 years). Twelve individuals (nine females) had symptoms attributed to hyperprolactinemia: menstruation-related abnormalities (n = 7), pubertal delay or arrest (n = 5), galactorrhea (n = 3), and decreased sexual functions (n = 2). MRI of the pituitary gland was obtained in 21 individuals; six had heterogeneity/hyperplasia of the gland, five had adenoma, and 10 had normal findings. Eleven individuals were treated with the dopamine agonist cabergoline, ameliorating the hyperprolactinemia-related symptoms in all those assessed. Routine monitoring of these symptoms together with prolactin concentrations, especially after the first decade of life, should be taken into consideration during follow-up evaluations. The potential of slow-release levodopa formulations and low-dose dopamine agonists as part of first-line therapy in the prevention and treatment of hyperprolactinemia should be investigated further in animal studies and human trials. This work adds hyperprolactinemia-related findings to the current knowledge of the phenotypic spectrum of inherited disorders of biogenic amine metabolism.

Hyperprolactinemia and male sexual function: focus on erectile dysfunction and sexual desire.

The present paper aims to analyze and discuss the available evidence supporting the relationship between male sexual function and elevated prolactin (PRL) levels (HPRL). Two different sources of data were analyzed. Clinical data were derived from a series of patients seeking medical care for sexual dysfunction at our Unit. Out of 418 studies, 25 papers were used with a meta-analytic approach to evaluate the overall prevalence of HPRL in patients with erectile dysfunction (ED) and to study the influence of HPRL and its treatment on male sexual function. Among 4215 patients (mean age 51.6 ± 13.1 years) consulting for sexual dysfunction at our Unit, 176 (4.2%) showed PRL levels above the normal range. Meta-analytic data showed that HPRL is a rare condition among patients with ED (2 [1;3]%). Either clinical and meta-analytic data confirm a stepwise negative influence of PRL on male sexual desire (S = 0.00004 [0.00003; 0.00006]; I = -0.58915 [-0.78438; -0.39392]; both p < 0.0001 from meta-regression analysis). Normalization of PRL levels is able to improve libido. The role of HPRL in ED remains inconclusive. Data from a meta-analytic approach showed that either HPRL or reduced T levels were independently associated with ED rates. The normalization of PRL levels only partially restored ED. HPRL did not significantly contribute to ED severity, in our clinical setting. In conclusion, treating HPRL can restore normal sexual desire, whereas its effect on erection is limited.

Improved Insulin Secretion Response and Beta-cell Function Correlated with Increased Prolactin Levels After Laparoscopic Sleeve Gastrectomy in Morbidly Obese Patients with Acanthosis Nigricans.

To explore insulin secretion patterns, β-cell function, and serum prolactin (PRL) concentrations in Chinese morbidly obese patients with Acanthosis nigricans (AN) and their alterations after laparoscopic sleeve gastrectomy (LSG). A total of 138 morbidly obese subjects undergoing LSG were categorized as simple obesity without AN (OB group, n = 55) and obesity with AN (AN group, n = 83). Oral glucose tolerance test (OGTT), PRL, and related metabolic indices were performed pre- and 12 months post-LSG. Insulin secretion patterns were derived from insulin secretion peak time during OGTT: type I (peak at 30 or 60 min) and type II (peak at 120 or 180 min). Preoperatively, AN group showed significantly higher proportions of type II insulin secretion pattern, fasting insulin (FINS), and homeostatic model assessment of insulin resistance (HOMA-IR) whereas lower oral glucose insulin sensitivity (OGIS), insulinogenic index (IGI), and disposition index (DI) than OB group, which were improved significantly at 12 months postoperatively in both groups, more pronounced in AN group. Intriguingly, serum PRL declined substantially in AN group than OB group at baseline whereas elevated only in the AN group post-LSG. After adjusting for confounding factors, elevated PRL correlated significantly with increased IGI and DI, and decreased HOMA-IR in both genders, as well as increased OGIS in females, which was detected only in the AN group CONCLUSION: Morbidly obese patients with AN presented delayed insulin secretion response, impaired insulin secretion, and β-cell dysfunction, which were significantly improved by LSG and might benefit from elevated PRL.

Multilineage Pituitary Neuroendocrine Tumors (PitNETs) Expressing PIT1 and SF1.

PitNETs are usually restricted in their cytodifferentiation to only one of 3 lineages dictated by expression of the pituitary transcription factors (TFs) PIT1, TPIT, or SF1. Tumors that show lineage infidelity and express multiple TFs are rare. We searched the pathology files of 4 institutions for PitNETs with coexpression of PIT1 and SF1. We identified 38 tumors in 21 women and 17 men, average age 53 (range 21-79) years. They represented 1.3 to 2.5% of PitNETs at each center. Acromegaly was the presentation in 26 patients; 2 had central hyperthyroidism associated with growth hormone (GH) excess and one had significantly elevated prolactin (PRL). The remainder had mass lesions with visual deficits, hypopituitarism, and/or headaches. Tumor size ranged from 0.9 to 5cm; all 7 lesions smaller than 1cm were associated with acromegaly. Larger lesions frequently invaded the cavernous sinuses. Four cases represented a second attempt at surgical resection. PIT1 was usually diffusely positive but 5 cases had variable (patchy or focal) staining. SF1 reactivity was variable in intensity but diffuse in all but 2 cases. GATA3 data, available in 14 cases, identified diffuse positivity in 5 and focal staining in 1. GH was expressed in all but 5 tumors, PRL and thyrotropin (TSH) were expressed in 14 and 13, respectively, follicle-stimulating hormone (FSH) in 11 of 18, and luteinizing hormone (LH) in 4 of 17. Keratin staining patterns were diffuse perinuclear/membranous in 27, variable perinuclear in 4, and negative in 3; scattered fibrous bodies were seen in 5 and diffuse fibrous bodies in 1. Ki67 labeling index ranged from < 1 to 7.9%. In 3 cases, these tumors represented one of multiple synchronous PitNETs; a separate corticotroph tumor was seen in 2 patients and one patient had 2 additional discrete lesions, a sparsely granulated lactotroph, and a pure gonadotroph tumor comprising a triple tumor. PitNETs expressing PIT1 and SF1 represent multilineage PitNETs. These rare tumors have variable clinical and morphological features, most often presenting as large tumors with GH excess and occasionally as one of multiple synchronous PitNETs of distinct lineages.

The Effect of Metformin on Plasma Prolactin Levels in Young Women with Autoimmune Thyroiditis.

Metformin decreases elevated prolactin levels, which are frequently found in patients with thyroid disorders. The aim of this study was to investigate whether thyroid autoimmunity modulates the impact of metformin on lactotrope secretory function. This study compared two matched groups of young women with prediabetes and mild-to-moderate prolactin excess: 28 subjects with coexisting euthyroid autoimmune thyroiditis (group 1) and 28 individuals without thyroid disorders (group 2), treated for six months with metformin (3 g daily). Thyroid antibody titers, glucose homeostasis markers, prolactin, thyrotropin, free thyroid hormones, FSH, LH, ACTH, IGF-1 and hsCRP were assessed at the beginning and at the end of the study. At entry, the study groups differed in antibody titers and hsCRP levels. Although the improvement in glucose homeostasis and the decrease in hsCRP levels were observed in both study groups, they were more pronounced in group 2. Only in group 2 did metformin reduce circulating prolactin levels (both total and monomeric). Prolactin-lowering properties of metformin positively correlated with baseline prolactin levels, baseline antibody titers (in group 1) and with the degree of reduction in hsCRP levels. The obtained results suggest that autoimmune thyroiditis may attenuate the impact of metformin on lactotrope secretory function.

Macroprolactinemia: a mini-review and update on clinical practice

Hyperprolactinemia is common among infertile patients, with up to 15%-20% of women with oligomenorrhea having hyperprolactinemia. Suppression of the hypothalamic-pituitary-gonadal axis via inhibition of pulsatile gonadotropin releasing hormone because of hyperprolactinemia is a common endocrine etiology of infertility. There are 3 forms of human prolactin (PRL): monomeric PRL, dimeric PRL, and macro-PRL. Also known as big-big PRL, macro-PRL has a molecular weight >150 kDa and normally comprises 5%-10% of circulating PRL. When the predominant form of circulating PRL is macro-PRL, macroprolactinemia is diagnosed. Among patients with hyperprolactinemia, 10%-46% have macroprolactinemia. Patients with macroprolactinemia are at risk of unnecessary pituitary imaging and treatment with dopamine agonists if not correctly diagnosed. Given the high prevalence of macroprolactinemia among patients with elevated PRL levels and the different management of patients with macroprolactinemia vs true monomeric hyperprolactinemia, all patients with persistently elevated PRL levels should be screened for macro-PRL.

Reproductive Function during Lactation

The phenomenon of locational amenorrhea, in which postpartum women experience temporary suppression of menstruation and fertility during breastfeeding, has long been recognized. This natural contraceptive effect is primarily attributed to elevated prolactin levels, which are stimulated by frequent suckling and inhibit the release of gonadotropinreleasing hormones and, subsequently, the menstrual cycle. However, the extent of lactational amenorrhea contraceptive efficacy varies among individuals owing to factors such as breastfeeding patterns, infant feeding behavior, and maternal health. Recent research has shed light on the underlying mechanisms governing the interplay between lactation and reproductive functions. Studies have shown that, while exclusively on-demand breastfeeding offers a higher level of contraceptive protection, introducing supplementary foods and reducing breastfeeding frequency can shorten the duration of lactational amenorrhea, potentially leading to earlier ovulation and conception. Additionally, the hormonal milieu during lactation may not be entirely suppressive, because occasional instances of follicular development and ovulation have been reported before the return of regular menstruation. Understanding the intricacies of reproductive function during lactation is important not only for family planning but also for optimizing maternal and infant health. The duration of exclusive breastfeeding has been associated with various health benefits for both the mother and the child, including enhanced immune protection, cognitive development, and a reduced risk of certain chronic diseases. Lactational amenorrhea serves as a physiological contraceptive method, but its efficacy is influenced by individual variations and breastfeeding practices. Further research is needed to elucidate the complex hormonal interactions and refine guidelines for optimal family planning during the postpartum period. Balancing the benefits of extended breastfeeding with a desire for family planning requires a comprehensive understanding of the intricate relationship between lactation and reproductive physiology

Vitamin D Status Determines Cardiometabolic Effects of Cabergoline in Women with Elevated Prolactin Levels: A Pilot Study.

Both hyperprolactinemia and vitamin D deficiency appear to be associated with increased cardiometabolic risk. This study aimed to determine whether vitamin D status influences the cardiometabolic effects of cabergoline. The study included three matched groups of women with mild to moderate hyperprolactinemia: vitamin D-naive subjects with vitamin D insufficiency (group A), women with vitamin D deficiency/insufficiency successfully treated with vitamin D (group B), and vitamin D-naive individuals with normal vitamin D status (group C). Plasma prolactin, 25-hydroxyvitamin D, estradiol, glucose homeostasis markers, lipids, high-sensitivity C-reactive protein (hsCRP), fibrinogen, homocysteine, and uric acid, as well as the urinary albumin-to-creatinine ratio (UACR), were measured at study entry and after four months of cabergoline treatment. Although cabergoline reduced prolactin levels and increased estradiol levels in all study groups, the effect on prolactin was more pronounced in groups B and C compared to group A. In groups B and C, the drug enhanced glucose homeostasis, increased HDL-cholesterol, and decreased triglycerides, hsCRP, fibrinogen, homocysteine, uric acid, and UACR. In group A, only insulin resistance, hsCRP, and homocysteine were reduced by cabergoline. The effects on insulin sensitivity, HDL-cholesterol, triglycerides, hsCRP, fibrinogen, homocysteine, uric acid, and UACR were proportional to the decrease in prolactin and baseline levels of 25-hydroxyvitamin D. The obtained results suggest that vitamin D status determines cabergoline's cardiometabolic effects.

A giant invasive macroprolactinoma with recurrent nasal bleeding as the first clinical presentation: case report and review of literature

BackgroundGiant prolactinoma (> 4 cm in dimension) is a rare disorder. Invasive macroprolactinoma has the potential to cause base of skull erosion and extend into the nasal cavity or even the sphenoid sinus. Nasal bleeding caused by intranasal tumor extension is a rare complication associated with invasive giant prolactinoma.We report a case of giant invasive macroprolactinoma with repeated nasal bleeding as the initial symptom.Case presentationA 24-year-old man with an invasive giant prolactinoma in the nasal cavity and sellar region who presented with nasal bleeding as the initial symptom, misdiagnosed as olfactory neuroblastoma. However, markedly elevated serum prolactin levels (4700 ng/mL), and a 7.8-cm invasive sellar mass confirmed the diagnosis of invasive giant prolactinoma. He was treated with oral bromocriptine. Serum prolactin was reduced to near normal after 6 months of treatment. Follow-up magnetic resonance imaging showed that the sellar lesion had disappeared completely and the skull base lesions were reduced.ConclusionThis case is notable in demonstrating the aggressive nature of untreated invasive giant prolactinomas which can cause a diagnostic difficulty with potential serious consequences. Early detection of hormonal levels can avoid unnecessary nasal biopsy. Early identification of pituitary adenoma with nasal bleeding as the first symptom is particularly important.

Abstract #1413579: Rathke Cleft Cyst Unveiling Incidental Prolactin Producing Adenoma

Rathke cleft cysts (RCCs) are benign sellar and or/suprasellar lesions that arise from remnants of Rathke's pouch. Pituitary hormonal dysfunction associated with RCCs most often present as hormonal deficiencies due to compression. However pituitary hyper-secretion may coexist with RCC challenging diagnosis and management. A 37-year-old female presented with worsening headache, bilateral blurry vision and pressure-like eye pain for two weeks. She denied any galactorrhea or irregular periods. Her medications included as-needed butalbital-acetaminophen-caffeine and alprazolam. CT Head without IV contrast revealed a pituitary lesion measuring 1.9 cm extending near the inferior margin of the optic chiasm. Subsequent MRI Pituitary with and without IV contrast revealed an enhancing sellar/suprasellar solid lesion measuring 1.6 x 2.7 x 1.9 cm with small hypoenhancing components associated with expansion of the sella, rightward infundibulum deviation, mass effect on the optic chiasm and left cavernous sinus invasion. Pituitary secretion workup revealed an elevated serum prolactin level of 50.4 ng/mL (range 4.8 - 23.3 ng/mL). Repeat prolactin level was 75.7 mg/ml. Dilution studies 1:10 and 1:100 revealed prolactin levels of 78.3 ng/mL and 75.9 ng/mL respectively; absence of hook effect. Her elevated prolactin was attributed to stalk effect given the large size of her sellar mass and relatively minimally elevated prolactin level. Serum Alpha Subunit, ILGF-1, TSH, FT4, LF, FSH, AM cortisol and ACTH level were all normal. She underwent endoscopic transsphenoidal pituitary mass resection with pathology results revealing prolactin producing adenoma and RCC. Immunostains were strongly positive for chromogranin A and prolactin while negative for FSH, ACTH, TSH, beta hCG, GH. Prolactin levels 11 days post-resection remained elevated at 50.7 ng/mL. She continued to have regular periods without galactorrhea. Additionally, she expressed desire to attain pregnancy. This case illustrates the presence of a secreting pituitary prolactinoma in the setting of an RCC. Whether these two entities share a common pathophysiology or simply co-exist is unknown. In one study of 33 surgically treated RCC at presentation, 60% had gonadotroph deficiency, 36% had ACTH deficiency, 36% had TSH deficiency, 18% had ADH deficiency and 31% had hyperprolactinemia (1). It is possible that the majority of this patient 's sellar mass was comprised of RCC as a much higher prolactin level would have been expect for the size of her mass. Interesting, her sellar mass exhibited enhancement which is uncharacteristic for RCC, classical described as cystic lesions without calcification or enhancement. Given that her post-resection prolactin level remained elevated and she desires pregnancy, she may require dopamine agonist therapy.

Effect of Curcumin (Standard and Supplement) with Zinc on Reproductive Hormones in Polycystic Ovary Syndrome (PCOS) Rats

Polycystic ovary syndrome (PCOS) is a complex and heterogeneous disorder that affects a large&nbsp;percentage of women worldwide. The pathophysiology is not fully explained. In recent years, complementary and alternative medicine has emerged as a viable treatment option. This study examined how curcumin and zinc affected on reproductive hormones in rats with polycystic ovary syndrome (PCOS). It was induced by oral administration of letrozole (1mg/kg/day) for 21 days. PCOS groups were treated over 14 days with curcumin standard 200 mg/kg, curcumin supplement 200 mg/kg, and zinc 30 mg /kg (separately or in combination with two forms of curcumin), and metformin 50 mg/kg as standard treatment. The blood biochemistry of these groups was compared to those of the groups of healthy, PCOS, and those who received metformin. The immunoassay ELISA technique was employed for measuring the concentration of reproductive hormones. The results manifested that the administration of letrozole resulted in a significant elevation (p≤0.05) of luteinizing hormone, follicle-stimulating hormone, testosterone, and prolactin associated with a significant decrease (p≤0.05) of estrogen and progesterone levels in the PCOS-designed model. The results of effect of curcumin supplement alone and with zinc showed a significant improvement in all parameters by reducing the luteinizing hormone, follicle-stimulating hormone, testosterone, and prolactin. Estrogen and progesterone elevated significantly for all groups, while the elevation was highly significant in both curcumin supplement alone and curcumin supplement with zinc. The treatment with curcumin supplement and their combination with zinc showed promising results in restoring reproductive hormones to the normal level.